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Find video protocols related to scientific articles indexed in Pubmed.
Plasma cytokine levels and risk of HIV-1 transmission and acquisition: a nested case-control study among HIV-1 serodiscordant couples.
J. Infect. Dis.
PUBLISHED: 11-13-2014
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?A heightened pro-inflammatory state has been hypothesized to enhance HIV-1 transmission - both susceptibility of HIV-1-exposed persons and infectiousness of HIV-1-infected persons.
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Single-agent tenofovir versus combination emtricitabine plus tenofovir for pre-exposure prophylaxis for HIV-1 acquisition: an update of data from a randomised, double-blind, phase 3 trial.
Lancet Infect Dis
PUBLISHED: 10-11-2014
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Antiretroviral pre-exposure prophylaxis (PrEP), with daily oral tenofovir disoproxil fumarate or tenofovir disoproxil fumarate in combination with emtricitabine, has been shown to be efficacious for HIV-1 prevention. Although the use of more than one antiretroviral agent is essential for effective HIV-1 treatment, more than one agent might not be required for effective prophylaxis. We assessed the efficacy of single-agent tenofovir disoproxil fumarate relative to combination emtricitabine plus tenofovir disoproxil fumarate as PrEP.
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Lay Social Resources for Support of Adherence to Antiretroviral Prophylaxis for HIV Prevention Among Serodiscordant Couples in sub-Saharan Africa: A Qualitative Study.
AIDS Behav
PUBLISHED: 10-01-2014
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Effectiveness of antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention will require high adherence. Using qualitative data, this paper identifies potential lay social resources for support of PrEP adherence by HIV serodiscordant couples in Uganda, laying the groundwork for incorporation of these resources into adherence support initiatives as part of implementation. The qualitative analysis characterizes support for PrEP adherence provided by HIV-infected spouses, children, extended family members, and the larger community. Results suggest social resources for support of PrEP adherence in Africa are plentiful outside formal health care settings and health systems and that couples will readily use them. The same shortage of health professionals that impeded scale-up of antiretroviral treatment for HIV/AIDS in Africa promises to challenge delivery of PrEP. Building on the treatment scale-up experience, implementers can address this challenge by examining the value of lay social resources for adherence support in developing strategies for delivery of PrEP.
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Pre-exposure prophylaxis does not affect the fertility of HIV-1-uninfected men.
AIDS
PUBLISHED: 09-27-2014
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There is a paucity of data on the effect of antiretroviral medications on male fertility. Couples affected by HIV-1 often have fertility intentions, and antiretroviral medications, as both treatment of HIV-1-infected persons and pre-exposure prophylaxis (PrEP) for uninfected persons, are part of peri-conception risk reduction.
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High medication adherence during periconception periods among HIV-1-uninfected women participating in a clinical trial of antiretroviral pre-exposure prophylaxis.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 08-15-2014
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Pre-exposure prophylaxis (PrEP) may be an important safer conception strategy for HIV-1-uninfected women with HIV-1-infected partners. Understanding medication adherence in this population may inform whether PrEP is a feasible safer conception strategy.
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Pregnancy incidence and outcomes among women receiving preexposure prophylaxis for HIV prevention: a randomized clinical trial.
JAMA
PUBLISHED: 07-20-2014
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Antiretroviral preexposure prophylaxis (PrEP), using tenofovir disoproxil fumarate (TDF) and combination emtricitabine/tenofovir disoproxil fumarate (FTC+TDF), is efficacious for prevention of human immunodeficiency virus (HIV) acquisition. PrEP could reduce periconception HIV risk, but the effect on pregnancy outcomes is not well defined.
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Daily oral tenofovir and emtricitabine-tenofovir preexposure prophylaxis reduces herpes simplex virus type 2 acquisition among heterosexual HIV-1-uninfected men and women: a subgroup analysis of a randomized trial.
Ann. Intern. Med.
PUBLISHED: 07-01-2014
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Daily oral preexposure prophylaxis (PrEP) using the antiretroviral tenofovir disoproxil fumarate (TDF) alone or in combination with emtricitabine (FTC-TDF) reduces the risk for HIV-1 acquisition. Tenofovir has in vitro activity against herpes simplex virus type 2 (HSV-2).
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HIV infection: epidemiology, pathogenesis, treatment, and prevention.
Lancet
PUBLISHED: 06-05-2014
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HIV prevalence is increasing worldwide because people on antiretroviral therapy are living longer, although new infections decreased from 3.3 million in 2002, to 2.3 million in 2012. Global AIDS-related deaths peaked at 2.3 million in 2005, and decreased to 1.6 million by 2012. An estimated 9.7 million people in low-income and middle-income countries had started antiretroviral therapy by 2012. New insights into the mechanisms of latent infection and the importance of reservoirs of infection might eventually lead to a cure. The role of immune activation in the pathogenesis of non-AIDS clinical events (major causes of morbidity and mortality in people on antiretroviral therapy) is receiving increased recognition. Breakthroughs in the prevention of HIV important to public health include male medical circumcision, antiretrovirals to prevent mother-to-child transmission, antiretroviral therapy in people with HIV to prevent transmission, and antiretrovirals for pre-exposure prophylaxis. Research into other prevention interventions, notably vaccines and vaginal microbicides, is in progress.
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Preferences for daily or intermittent pre-exposure prophylaxis regimens and ability to anticipate sex among HIV uninfected members of Kenyan HIV serodiscordant couples.
AIDS Behav
PUBLISHED: 05-30-2014
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Intermittent dosing for pre-exposure prophylaxis (PrEP) has been proposed as an alternative to daily PrEP to reduce cost and patient drug exposure and to improve adherence. One possible dosing regimen is pre-intercourse PrEP, which requires anticipating sex in advance. We examined preferences for daily versus pre-intercourse PrEP and ability to anticipate sex among 310 HIV uninfected members of HIV serodiscordant heterosexual couples in Thika, Kenya, with high HIV knowledge and experience with daily PrEP use in a clinical trial setting. Preferences were evenly split between daily PrEP (47.4 %) and pre-intercourse PrEP (50.7 %). Participants were more likely to prefer daily PrEP if they reported unprotected sex during the prior month (adjusted prevalence ratio [aPR] 1.48, 95 % CI 1.20-1.81) or <80 % adherence to study drug (aPR 1.50, 95 % CI 1.25-1.79), and were less likely to prefer daily PrEP if sex was usually planned, versus spontaneous (aPR 0.76, 95 % CI 0.61-0.96). A minority (24.2 %) reported anticipating sex >3 h in advance, with younger participants being less likely to do so (aPR 0.43, 95 % CI 0.23-0.83 for ages 18-29 vs. ?40). Findings suggest that intermittent PrEP could be a popular option in this population, but that optimal adherence and sufficient drug levels might be challenging with a pre-intercourse regimen.
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An intervention to support HIV preexposure prophylaxis adherence in HIV-serodiscordant couples in Uganda.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 05-24-2014
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Daily preexposure prophylaxis (PrEP) is an effective HIV prevention strategy, but adherence is required for maximum benefit. To date, there are no empirically supported PrEP adherence interventions. This article describes the process of developing a PrEP adherence intervention and presents results on its impact on adherence.
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Successful discontinuation of the placebo arm and provision of an effective HIV prevention product after a positive interim efficacy result: the partners PrEP study experience.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 05-16-2014
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Dissemination of research results to study participants and stakeholders and provision of proven effective products in the immediate post-trial period are core elements of the conduct of biomedical HIV prevention clinical trials. Few biomedical HIV prevention trials have demonstrated HIV protection with novel interventions, and thus, communication of positive trial results and provision of an effective product have not been tested in many situations.
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Delay of antiretroviral therapy initiation is common in East African HIV-infected individuals in serodiscordant partnerships.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 05-07-2014
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WHO guidance recommends antiretroviral therapy (ART) initiation for all persons with a known HIV-uninfected partner, as a strategy to prevent HIV transmission. Uptake of ART among HIV-infected partners in serodiscordant partnerships is not known, which we evaluated in African HIV serodiscordant couples.
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HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 05-03-2014
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Antiretroviral pre-exposure prophylaxis (PrEP) is a novel HIV prevention strategy for which adherence is a known determinant of efficacy. Blood concentrations of PrEP medications are one objective marker of adherence.
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My intention was a child but I was very afraid: fertility intentions and HIV risk perceptions among HIV-serodiscordant couples experiencing pregnancy in Kenya.
AIDS Care
PUBLISHED: 04-29-2014
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We sought to understand fertility intentions and HIV risk considerations among Kenyan HIV-serodiscordant couples who became pregnant during a prospective study. We conducted individual in-depth interviews (n = 36) and focus group discussions (n = 4) and performed qualitative data analysis and interpretation using an inductive approach. Although most of the couples were aware of the risk of horizontal and vertical HIV transmission, almost all couples reported that they had intended to become pregnant and that the desire for children superseded HIV risk considerations. Motivations for pregnancy were numerous and complex: satisfying desired family size, desire for biological children, maintaining stability of the union, and sociocultural pressures. Couples desired strategies to reduce HIV risk during conception, but expressed hesitation toward assisted reproductive technologies as unnatural. HIV prevention programs should therefore address conception desires and counsel about coordinated periconception risk-reduction strategies.
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Variants in host viral replication cycle genes are associated with heterosexual HIV-1 acquisition in Africans.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 01-28-2014
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We evaluated genetic variants in 51 candidate genes encoding proteins that interact with HIV-1 during the virus life cycle for association with HIV-1 outcomes in an African cohort.
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A prospective study of the effect of pregnancy on CD4 counts and plasma HIV-1 RNA concentrations of antiretroviral-naive HIV-1-infected women.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 01-21-2014
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In HIV-1-infected women, CD4 count declines occur during pregnancy, which has been attributed to hemodilution. However, for women who have not initiated antiretroviral therapy, it is unclear if CD4 declines are sustained beyond pregnancy and accompanied by increased viral levels, which could indicate an effect of pregnancy on accelerating HIV-1 disease progression.
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HIV-1 subtype C is not associated with higher risk of heterosexual HIV-1 transmission: a multinational study among HIV-1 serodiscordant couples.
AIDS
PUBLISHED: 01-14-2014
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HIV-1 subtype C has emerged as the most prevalent strain of HIV-1 worldwide, leading to speculation that subtype C may be more transmissible than other subtypes. We compared the risk of HIV-1 transmission for subtype C versus non-C subtypes (A, D, G and recombinant forms) among heterosexual African HIV-1 serodiscordant couples.
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'If I am given antiretrovirals I will think I am nearing the grave': Kenyan HIV serodiscordant couples' attitudes regarding early initiation of antiretroviral therapy.
AIDS
PUBLISHED: 01-14-2014
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Early initiation of antiretroviral therapy (ART) - that is, at higher CD4 cell counts (>350?cells/?l) - is a potent HIV prevention strategy. The WHO recommends ART initiation by all HIV-infected individuals in HIV serodiscordant relationships to prevent HIV transmission, yet the acceptability of early ART among couples has not been well studied.
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A comparison of two measures of HIV diversity in multi-assay algorithms for HIV incidence estimation.
PLoS ONE
PUBLISHED: 01-01-2014
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Multi-assay algorithms (MAAs) can be used to estimate HIV incidence in cross-sectional surveys. We compared the performance of two MAAs that use HIV diversity as one of four biomarkers for analysis of HIV incidence.
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Toll-like receptor polymorphism associations with HIV-1 outcomes among sub-Saharan Africans.
J. Infect. Dis.
PUBLISHED: 12-10-2013
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Objective.?We evaluated Toll-like receptors (TLRs) single nucleotide polymorphisms (SNPs) for associations with HIV-1 acquisition, set-point and disease progression in African couples.Methods.?Seven candidate and 116 haplotype-tagging SNPs (tagSNPs) were genotyped in 504 HIV-1 infected cases, and 343 seronegative controls.Results.?TLR9 1635A/G was associated with reduced HIV-1 acquisition among HIV-seronegative controls with high but not low HIV-1 exposure (odds ratio [OR]=0.7; p=0.03 and OR=0.9, p=0.5, respectively). TLR7 rs179012 and TLR2 597C/T reduced set-point; the latter modified by time since HIV-1 acquisition. TLR8 1A/G reduced disease progression.Conclusion.?TLR SNPs impact HIV-1 outcomes with epidemiologic factors modifying these relationships.
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Efficacy of preexposure prophylaxis for HIV-1 prevention among high-risk heterosexuals: subgroup analyses from a randomized trial.
AIDS
PUBLISHED: 11-11-2013
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Daily oral antiretroviral preexposure prophylaxis (PrEP) is a promising strategy for prevention of HIV-1 acquisition. Three clinical trials demonstrated PrEP efficacy; however, two PrEP trials among women did not find protection against HIV-1. One hypothesis proposed for these divergent results is that PrEP efficacy may be reduced in populations with higher HIV-1 incidence.
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HIV Diversity as a Biomarker for HIV Incidence Estimation: Including a High-Resolution Melting Diversity Assay in a Multiassay Algorithm.
J. Clin. Microbiol.
PUBLISHED: 10-23-2013
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Multiassay algorithms (MAAs) can be used to estimate cross-sectional HIV incidence. We previously identified a robust MAA that includes the BED capture enzyme immunoassay (BED-CEIA), the Bio-Rad Avidity assay, viral load, and CD4 cell count. In this report, we evaluated MAAs that include a high-resolution melting (HRM) diversity assay that does not require sequencing. HRM scores were determined for eight regions of the HIV genome (2 in gag, 1 in pol, and 5 in env). The MAAs that were evaluated included the BED-CEIA, the Bio-Rad Avidity assay, viral load, and the HRM diversity assay, using HRM scores from different regions and a range of region-specific HRM diversity assay cutoffs. The performance characteristics based on the proportion of samples that were classified as MAA positive by duration of infection were determined for each MAA, including the mean window period. The cross-sectional incidence estimates obtained using optimized MAAs were compared to longitudinal incidence estimates for three cohorts in the United States. The performance of the HRM-based MAA was nearly identical to that of the MAA that included CD4 cell count. The HRM-based MAA had a mean window period of 154 days and provided cross-sectional incidence estimates that were similar to those based on cohort follow-up. HIV diversity is a useful biomarker for estimating HIV incidence. MAAs that include the HRM diversity assay can provide accurate HIV incidence estimates using stored blood plasma or serum samples without a requirement for CD4 cell count data.
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Sexual behaviour of heterosexual men and women receiving antiretroviral pre-exposure prophylaxis for HIV prevention: a longitudinal analysis.
Lancet Infect Dis
PUBLISHED: 10-17-2013
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Scarce data are available to assess sexual behaviour of individuals using antiretroviral pre-exposure prophylaxis for HIV prevention. Increased sexual risk taking by individuals using effective HIV prevention strategies, like pre-exposure prophylaxis, could offset the benefits of HIV prevention. We studied whether the use of pre-exposure prophylaxis in HIV-uninfected men and women in HIV-serodiscordant couples was associated with increased sexual risk behaviour.
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Adherence to antiretroviral prophylaxis for HIV prevention: a substudy cohort within a clinical trial of serodiscordant couples in East Africa.
PLoS Med.
PUBLISHED: 09-01-2013
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Randomized clinical trials of oral antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention have widely divergent efficacy estimates, ranging from 0% to 75%. These discrepancies are likely due to differences in adherence. To our knowledge, no studies to date have examined the impact of improving adherence through monitoring and/or intervention, which may increase PrEP efficacy, or reported on objective behavioral measures of adherence, which can inform PrEP effectiveness and implementation.
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An empiric risk scoring tool for identifying high-risk heterosexual HIV-1-serodiscordant couples for targeted HIV-1 prevention.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 08-21-2013
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Heterosexual HIV-1-serodiscordant couples are increasingly recognized as an important source of new HIV-1 infections in sub-Saharan Africa. A simple risk assessment tool could be useful for identifying couples at highest risk for HIV-1 transmission.
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Correlation between pill counts and biologic effects in an HIV-1 prevention clinical trial: implications for measuring adherence.
AIDS Behav
PUBLISHED: 08-07-2013
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Clinic-based pill counts of unused study medication are frequently used to measure adherence in HIV-1 prevention trials. Monthly pill count adherence data from the Partners in Prevention HSV/HIV Transmission Study, a double-blind, placebo controlled trial of twice-daily acyclovir suppression of herpes simplex virus type 2 (HSV-2) in HIV-1 infected persons was used to compare changes between 3,381 placebo and active arm participants in two objective biologic measures of acyclovirs drug activity: reduction in plasma HIV-1 RNA and HSV-2 genital ulcer disease (GUD). Higher acyclovir pill count adherence was associated with greater reductions in plasma HIV-1 RNA and GUD, indicating pill count data is strongly correlated with biological effects of adherence. However, when calculated adherence exceeded 102 % (i.e., fewer pills returned than expected) and when pill counts were missing because bottles were not returned, plasma HIV-1 RNA and GUD effects were diminished, likely indicating periods of non-adherence.
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Daily acyclovir to decrease herpes simplex virus type 2 (HSV-2) transmission from HSV-2/HIV-1 coinfected persons: a randomized controlled trial.
J. Infect. Dis.
PUBLISHED: 07-30-2013
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Daily suppressive therapy with valacyclovir reduces risk of sexual transmission of herpes simplex virus type 2 (HSV-2) in HSV-2-serodiscordant heterosexual couples by 48%. Whether suppressive therapy reduces HSV-2 transmission from persons coinfected with HSV-2 and human immunodeficiency virus type 1 (HIV-1) is unknown.
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Summary measures of adherence using pill counts in two HIV prevention trials: the need for standardisation in reporting.
AIDS Behav
PUBLISHED: 06-27-2013
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For trials of user-dependent HIV prevention products, accurate adherence measurements are essential to interpret and compare results across trials. We used pill count data from two recent HIV prevention trials of herpes simplex virus type 2 (HSV-2) suppression, to show that estimates of adherence vary substantially depending on assumptions that are made in analysing pill count data. We associate calculated adherence with biological markers of anti-HSV-2 activity. In both trials, calculated adherence varied considerably, depending on the summary measure used, and the handling of intervals with apparent over-adherence (fewer pills returned than expected), and unreturned pills. Intervals of apparent over-adherence were associated with reduced antiviral effects on biological markers of herpes reactivation, indicating these are likely to represent periods of non-adherence. Our results demonstrate the clear need for standardisation in reporting of adherence data that are based on pill counts.
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Integrated strategies for combination HIV prevention: principles and examples for men who have sex with men in the Americas and heterosexual African populations.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 06-15-2013
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Combination HIV prevention is of high priority for increasing the impact of partially efficacious HIV prevention interventions for specific populations and settings. Developing the package requires critical review of local epidemiology of HIV infection regarding most-impacted populations and those at high risk of HIV transmission and acquisition, drivers of HIV infection, and available interventions to address these risk factors. Interventions should be considered in terms of the evidence basis for efficacy, potential synergies, and feasibility of delivery at scale, which is important to achieve high coverage and impact, coupled with high acceptability to populations, which will impact uptake, adherence, and retention. Evaluation requires process measures of uptake, adherence, retention, and outcome measures of reduction in HIV infectiousness and acquisition. Three examples of combination prevention concepts are summarized for men who have sex with men in the Americas, young women in sub-Saharan Africa, and HIV serodiscordant couples.
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Hormonal contraceptive use and risk of HIV-1 disease progression.
AIDS
PUBLISHED: 06-14-2013
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For HIV-1-infected women, hormonal contraception prevents unintended pregnancy, excess maternal morbidity, and vertical HIV-1 transmission. Hormonal contraceptives are widely used but their effects on HIV-1 disease progression are unclear.
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Partner characteristics predicting HIV-1 set point in sexually acquired HIV-1 among African seroconverters.
AIDS Res. Hum. Retroviruses
PUBLISHED: 06-06-2013
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Plasma HIV-1 RNA set point is an important predictor of HIV-1 disease progression. We hypothesized that inoculum size and HIV-1 exposure prior to HIV-1 transmission may modulate set point. We evaluated predictors of set point among 141 African HIV-1 seroconverters and their HIV-1-infected study partners. We compared characteristics of seroconverters and their HIV-1-infected partners and HIV-1 set point. Data were from a clinical trial of genital HSV-2 suppression with acyclovir to reduce HIV-1 transmission in HIV-1 serodiscordant couples with HIV-1 transmission linkage assigned through virus sequencing. Our analysis includes data from all transmissions including those with transmission linkage to the HIV-1-infected "source partner" and those that were not linked to their HIV-1-infected study partner. In multivariable analysis, higher plasma HIV-1 in source partners was associated with higher seroconverter set point ( + 0.44 log10 copies/ml per log(10) source partner plasma HIV-1, p < 0.001). In addition, bacterial vaginosis (BV) among female source partners near the time of infection was associated with higher set point in their male seroconverters ( + 0.49 log(10), p = 0.04). Source partner characteristics associated with lower set point included male circumcision ( - 0.63 log(10), p = 0.03) and assignment to acyclovir ( - 0.44 log10, p = 0.02). The proportion of variation in set point explained by plasma HIV-1 RNA of the source partner, after controlling for other factors, was 0.06. Source partner plasma HIV-1 level is the most significant predictor of seroconverter set point, possibly reflecting characteristics of the transmitted virus. Acyclovir use, BV among women source partners, and circumcision among male source partners may alter the set point by affecting transmitted virus inoculum in the source partners genital compartment.
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High HIV testing uptake and linkage to care in a novel program of home-based HIV counseling and testing with facilitated referral in KwaZulu-Natal, South Africa.
J. Acquir. Immune Defic. Syndr.
PUBLISHED: 05-30-2013
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For antiretroviral therapy (ART) to have a population-level HIV prevention impact, high levels of HIV testing and effective linkages to HIV care among HIV-infected persons are required.
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Daily short message service surveys to measure sexual behavior and pre-exposure prophylaxis use among Kenyan men and women.
AIDS Behav
PUBLISHED: 05-23-2013
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Pre-exposure prophylaxis (PrEP) is a novel HIV prevention strategy which requires high adherence. We tested the use of daily short message service (i.e., SMS/text message) surveys to measure sexual behavior and PrEP adherence in Kenya. Ninety-six HIV-uninfected adult individuals, taking daily oral PrEP in a clinical trial, received daily SMS surveys for 60 days. Most participants (96.9 %) reported taking PrEP on ?80 % days, but 69.8 % missed at least one dose. Unprotected sex was reported on 4.9 % of days; however, 47.9 % of participants reported unprotected sex at least once. Unprotected sex was not correlated with PrEP use (OR = 0.95). Participants reporting more sex were less likely to report PrEP non-adherence and those reporting no sex were most likely to report missing a PrEP dose (adjusted OR = 1.87). PrEP adherence was high, missed doses were correlated with sexual abstinence, and unprotected sex was not associated with decreased PrEP adherence.
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Understanding the potential impact of a combination HIV prevention intervention in a hyper-endemic community.
PLoS ONE
PUBLISHED: 01-23-2013
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Despite demonstrating only partial efficacy in preventing new infections, available HIV prevention interventions could offer a powerful strategy when combined. In anticipation of combination HIV prevention programs and research studies we estimated the population-level impact of combining effective scalable interventions at high population coverage, determined the factors that influence this impact, and estimated the synergy between the components.
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Plasma viral loads during early HIV-1 infection are similar in subtype C- and non-subtype C-infected African seroconverters.
J. Infect. Dis.
PUBLISHED: 01-11-2013
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Recent data suggest that infection with human immunodeficiency virus type 1 (HIV-1) subtype C results in prolonged high-level viremia (>5 log10 copies/mL) during early infection. We examined the relationship between HIV-1 subtype and plasma viremia among 153 African seroconverters. Mean setpoint viral loads were similar for C and non-C subtypes: 4.36 vs 4.42 log10 copies/mL (P = .61). The proportion of subtype C-infected participants with viral loads >5 log10 copies/mL was not greater than the proportion for those with non-C infection. Our data do not support the hypothesis that higher early viral load accounts for the rapid spread of HIV-1 subtype C in southern Africa.
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Performance of a Limiting-Antigen Avidity Enzyme Immunoassay for Cross-Sectional Estimation of HIV Incidence in the United States.
PLoS ONE
PUBLISHED: 01-01-2013
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A limiting antigen avidity enzyme immunoassay (HIV-1 LAg-Avidity assay) was recently developed for cross-sectional HIV incidence estimation. We evaluated the performance of the LAg-Avidity assay alone and in multi-assay algorithms (MAAs) that included other biomarkers.
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Development of Methods for Cross-Sectional HIV Incidence Estimation in a Large, Community Randomized Trial.
PLoS ONE
PUBLISHED: 01-01-2013
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Accurate methods of HIV incidence determination are critically needed to monitor the epidemic and determine the population level impact of prevention trials. One such trial, Project Accept, a Phase III, community-randomized trial, evaluated the impact of enhanced, community-based voluntary counseling and testing on population-level HIV incidence. The primary endpoint of the trial was based on a single, cross-sectional, post-intervention HIV incidence assessment.
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A qualitative study of barriers to consistent condom use among HIV-1 serodiscordant couples in Kenya.
AIDS Care
PUBLISHED: 11-15-2011
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This study explored barriers to consistent condom use among heterosexual HIV-1 serodiscordant couples who were aware of the HIV-1 serodiscordant status and had been informed about condom use as a risk reduction strategy. We conducted 28 in-depth interviews and 9 focus group discussions among purposively selected heterosexual HIV-1 serodiscordant couples from Thika and Nairobi districts in Kenya. We analyzed the transcribed data with a grounded theory approach. The most common barriers to consistent condom use included male partners reluctance to use condoms regardless of HIV-1 status coupled with female partners inability to negotiate condom use, misconceptions about HIV-1 serodiscordance, and desire for children. Specific areas of focus should include development of skills for women to effectively negotiate condom use, ongoing information on HIV-1 serodiscordance and education on safer conception practices that minimize risk of HIV-1 transmission.
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High-dose valacyclovir HSV-2 suppression results in greater reduction in plasma HIV-1 levels compared with standard dose acyclovir among HIV-1/HSV-2 coinfected persons: a randomized, crossover trial.
J. Infect. Dis.
PUBLISHED: 10-12-2011
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Standard-dose HSV-2 suppressive therapy (acyclovir 400 mg twice daily) reduces plasma HIV-1 levels by 0.25-0.50 log(10) copies/mL. It is not known if higher doses might further suppress HIV-1 levels.
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Use of hormonal contraceptives and risk of HIV-1 transmission: a prospective cohort study.
Lancet Infect Dis
PUBLISHED: 10-03-2011
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Hormonal contraceptives are used widely but their effects on HIV-1 risk are unclear. We aimed to assess the association between hormonal contraceptive use and risk of HIV-1 acquisition by women and HIV-1 transmission from HIV-1-infected women to their male partners.
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A post-trial assessment of factors influencing study drug adherence in a randomized biomedical HIV-1 prevention trial.
AIDS Behav
PUBLISHED: 08-25-2011
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High adherence and maintenance of blinding are critical for placebo-controlled efficacy trials of HIV-1 biomedical prevention strategies. We assessed adherence to study drug and factors affecting adherence, including perceived randomization group, in a post-trial questionnaire of participants who completed HPTN 039, a randomized, placebo-controlled trial of HSV-2 suppression with twice-daily acyclovir to reduce HIV-1 acquisition. Of the 3172 trial participants, 2003 (63%) completed the post-trial questionnaire. Of these 2003, 72% reported missing a dose of study drug less than twice a week. Study drug adherence was not compromised by perceived randomization or genital ulcer symptoms during the study. Alcohol use was cited as an adherence barrier in some populations. Assessment of study drug adherence during and at the end of trials can evaluate perceptions of randomization and adherence by randomization arm, help to better understand barriers to and motivations for adherence, and develop interventions to increase adherence for future trials.
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Treatment with valacyclovir, famciclovir, or antiretrovirals reduces human herpesvirus-8 replication in HIV-1 seropositive men.
J. Med. Virol.
PUBLISHED: 08-13-2011
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Human herpesvirus-8 (HHV-8) replication is a key factor in Kaposi sarcoma, primary effusion lymphoma, and Castleman disease pathogenesis. In vitro data suggest that antivirals inhibit HHV-8 replication, but little data exist in humans. Daily oropharyngeal swabs were analyzed from HIV/HHV-8 dually infected men enrolled in three previous clinical trials of valacyclovir and famciclovir for HIV-1 and/or HSV-2 suppression. Fifty-eight participants contributed 6,036 swabs. HHV-8 was detected in 1,128 (19%) of 6,036 swabs, including 618 (21%) of 2,992 on placebo, 323 (15%) of 2,221 on valacyclovir, and 187 (23%) of 823 on famciclovir. After adjusting for baseline HIV viral load and highly active antiretroviral therapy (HAART) use, an 18% reduction in HHV-8 shedding frequency (IRR 0.822; P?=?0.011) was found in participants on valacyclovir and a 30% reduction (IRR 0.700; P?
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A prospective study of frequency and correlates of intimate partner violence among African heterosexual HIV serodiscordant couples.
AIDS
PUBLISHED: 08-04-2011
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Intimate partner violence (IPV) is common worldwide and is an important consideration in couples HIV voluntary counseling and testing (CVCT), especially for HIV-serodiscordant couples (i.e. in which only one member is HIV-infected).
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Increased risk of HIV-1 transmission in pregnancy: a prospective study among African HIV-1-serodiscordant couples.
AIDS
PUBLISHED: 07-26-2011
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Physiologic and behavioral changes during pregnancy may alter HIV-1 susceptibility and infectiousness. Prospective studies exploring pregnancy and HIV-1 acquisition risk in women have found inconsistent results. No study has explored the effect of pregnancy on HIV-1 transmission risk from HIV-1-infected women to male partners.
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Use of a high resolution melting (HRM) assay to compare gag, pol, and env diversity in adults with different stages of HIV infection.
PLoS ONE
PUBLISHED: 07-20-2011
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Cross-sectional assessment of HIV incidence relies on laboratory methods to discriminate between recent and non-recent HIV infection. Because HIV diversifies over time in infected individuals, HIV diversity may serve as a biomarker for assessing HIV incidence. We used a high resolution melting (HRM) diversity assay to compare HIV diversity in adults with different stages of HIV infection. This assay provides a single numeric HRM score that reflects the level of genetic diversity of HIV in a sample from an infected individual.
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Characteristics of HIV-1 serodiscordant couples enrolled in a clinical trial of antiretroviral pre-exposure prophylaxis for HIV-1 prevention.
PLoS ONE
PUBLISHED: 07-06-2011
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Stable heterosexual HIV-1 serodiscordant couples in Africa have high HIV-1 transmission rates and are a critical population for evaluation of new HIV-1 prevention strategies. The Partners PrEP Study is a randomized, double-blind, placebo-controlled trial of tenofovir and emtricitabine-tenofovir pre-exposure prophylaxis to decrease HIV-1 acquisition within heterosexual HIV-1 serodiscordant couples. We describe the trial design and characteristics of the study cohort.
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Genomewide association study for determinants of HIV-1 acquisition and viral set point in HIV-1 serodiscordant couples with quantified virus exposure.
PLoS ONE
PUBLISHED: 06-08-2011
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Host genetic factors may be important determinants of HIV-1 sexual acquisition. We performed a genome-wide association study (GWAS) for host genetic variants modifying HIV-1 acquisition and viral control in the context of a cohort of African HIV-1 serodiscordant heterosexual couples. To minimize misclassification of HIV-1 risk, we quantified HIV-1 exposure, using data including plasma HIV-1 concentrations, gender, and condom use.
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Male circumcision and risk of HIV acquisition among MSM.
AIDS
PUBLISHED: 06-07-2011
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To assess the association between male circumcision, insertive anal sex practices, and HIV acquisition in a cohort of MSM.
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Combination HIV prevention: significance, challenges, and opportunities.
Curr HIV/AIDS Rep
PUBLISHED: 05-27-2011
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No single HIV prevention strategy will be sufficient to control the HIV pandemic. However, a growing number of interventions have shown promise in partially protecting against HIV transmission and acquisition, including knowledge of HIV serostatus, behavioral risk reduction, condoms, male circumcision, needle exchange, treatment of curable sexually transmitted infections, and use of systemic and topical antiretroviral medications by both HIV-infected and uninfected persons. Designing the optimal package of interventions that matches the epidemiologic profile of a target population, delivering that package at the population level, and evaluating safety, acceptability, coverage, and effectiveness, all involve methodological challenges. Nonetheless, there is an unprecedented opportunity to develop "prevention packages" that combine various arrays of evidence-based strategies, tailored to the needs of diverse subgroups and targeted to achieve high coverage for a measurable reduction in population-level HIV transmission. HIV prevention strategies that combine partially effective interventions should be scaled up and evaluated.
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Serological immunity to adenovirus serotype 5 is not associated with risk of HIV infection: a case-control study.
AIDS
PUBLISHED: 05-07-2011
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adenoviruses are among the most promising vectors for the development of an HIV vaccine. The results of the phase IIB study of the adenovirus serotype 5-based Merck Trivalent HIV vaccine have raised the concern that serological immunity to adenovirus serotype 5 (Ad5) could be linked to HIV acquisition risk in high-risk individuals. We examined the association between adenovirus serostatus and the rate of incident HIV infection in populations at elevated risk of HIV acquisition.
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Circumcision of male children for reduction of future risk for HIV: acceptability among HIV serodiscordant couples in Kampala, Uganda.
PLoS ONE
PUBLISHED: 04-26-2011
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The ultimate success of medical male circumcision for HIV prevention may depend on targeting male infants and children as well as adults, in order to maximally reduce new HIV infections into the future.
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Genital HIV-1 RNA predicts risk of heterosexual HIV-1 transmission.
Sci Transl Med
PUBLISHED: 04-08-2011
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High plasma HIV-1 RNA concentrations are associated with an increased risk of HIV-1 transmission. Although plasma and genital HIV-1 RNA concentrations are correlated, no study has evaluated the relationship between genital HIV-1 RNA and the risk of heterosexual HIV-1 transmission. In a prospective study of 2521 African HIV-1 serodiscordant couples, we assessed genital HIV-1 RNA quantity and HIV-1 transmission risk. HIV-1 transmission linkage was established within the partnership by viral sequence analysis. We tested endocervical samples from 1805 women, including 46 who transmitted HIV-1 to their partner, and semen samples from 716 men, including 32 who transmitted HIV-1 to their partner. There was a correlation between genital and plasma HIV-1 RNA concentrations: For endocervical swabs, Spearmans rank correlation coefficient ? was 0.56, and for semen, ? was 0.55. Each 1.0 log(10) increase in genital HIV-1 RNA was associated with a 2.20-fold (for endocervical swabs: 95% confidence interval, 1.60 to 3.04) and a 1.79-fold (for semen: 95% confidence interval, 1.30 to 2.47) increased risk of HIV-1 transmission. Genital HIV-1 RNA independently predicted HIV-1 transmission risk after adjusting for plasma HIV-1 quantity (hazard ratio, 1.67 for endocervical swabs and 1.68 for semen). Seven female-to-male and four male-to-female HIV-1 transmissions (incidence <1% per year) occurred from persons with undetectable genital HIV-1 RNA, but in all 11 cases, plasma HIV-1 RNA was detected. Thus, higher genital HIV-1 RNA concentrations are associated with greater risk of heterosexual HIV-1 transmission, and this effect was independent of plasma HIV-1 concentrations. These data suggest that HIV-1 RNA in genital secretions could be used as a marker of HIV-1 sexual transmission risk.
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HIV preexposure prophylaxis: new data and potential use.
Top Antivir Med
PUBLISHED: 04-07-2011
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HIV preexposure prophylaxis (PrEP) has demonstrated efficacy in 4 studies: 1) the CAPRISA 004 trial of pericoital administration of 1% tenofovir gel showed moderate (39%) efficacy in reducing risk of HIV acquisition in young women; 2) the iPrEx trial of daily oral emtricitabine/tenofovir had moderate (44%) efficacy in reducing risk of HIV acquisition among high-risk men who have sex with men (MSM); 3) the Partners PrEP Study in African HIV-serodiscordant couples, in which the HIV-seronegative partner received daily oral tenofovir or emtricitabine/tenofovir, showed high efficacy (62% and 73%, respectively); and 4) the TDF2 trial in young heterosexual men and women in Botswana demonstrated 62% efficacy of daily oral emtricitabine/tenofovir. Greater adherence to PrEP is associated with greater efficacy. Resistance to tenofovir and emtricitabine have been rare and were primarily observed during PrEP initiation in those with acute HIV infection. PrEP has been found to be safe and well tolerated. The FEM-PrEP trial of oral emtricitabine/tenofovir and the VOICE trials of daily 1% tenofovir gel and oral tenofovir (both studies conducted in African women) did not show protective benefit, for reasons that currently remain unknown. The Bangkok Tenofovir Study of oral tenofovir in injection drug users, and the emtricitabine/tenofovir study arm of the VOICE trial, are ongoing. Establishing PrEP programs will be a great challenge and a great opportunity. This article summarizes a presentation by Connie L. Celum, MD, MPH, at the IAS-USA live continuing education course held in Chicago in June 2011, and includes updates on PrEP trial results reported since July 2011.
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Risk Factors for HSV-2 Infection among Sexual Partners of HSV-2/HIV-1 Co-Infected Persons.
BMC Res Notes
PUBLISHED: 03-01-2011
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Herpes simplex virus type 2 (HSV-2) is the most frequent cause of genital ulcer disease worldwide and has been associated with increased risk for HIV-1 acquisition and transmission. We conducted a cross-sectional analysis of risk factors for HSV-2 infection among HIV-1 uninfected partners, whose partners were co-infected with HIV-1 and HSV-2.
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Optimal uses of antiretrovirals for prevention in HIV-1 serodiscordant heterosexual couples in South Africa: a modelling study.
PLoS Med.
PUBLISHED: 02-22-2011
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Antiretrovirals have substantial promise for HIV-1 prevention, either as antiretroviral treatment (ART) for HIV-1-infected persons to reduce infectiousness, or as pre-exposure prophylaxis (PrEP) for HIV-1-uninfected persons to reduce the possibility of infection with HIV-1. HIV-1 serodiscordant couples in long-term partnerships (one member is infected and the other is uninfected) are a priority for prevention interventions. Earlier ART and PrEP might both reduce HIV-1 transmission in this group, but the merits and synergies of these different approaches have not been analyzed.
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Performance of the Focus HerpeSelect-2 enzyme immunoassay for the detection of herpes simplex virus type 2 antibodies in seven African countries.
Sex Transm Infect
PUBLISHED: 02-09-2011
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To compare the performance of the Focus HerpeSelect-2 enzyme immunoassay (EIA) with the gold standard herpes simplex virus (HSV) type 2 western blot, among HIV-1-uninfected men and women in east and southern Africa.
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Viral linkage in HIV-1 seroconverters and their partners in an HIV-1 prevention clinical trial.
PLoS ONE
PUBLISHED: 01-18-2011
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Characterization of viruses in HIV-1 transmission pairs will help identify biological determinants of infectiousness and evaluate candidate interventions to reduce transmission. Although HIV-1 sequencing is frequently used to substantiate linkage between newly HIV-1 infected individuals and their sexual partners in epidemiologic and forensic studies, viral sequencing is seldom applied in HIV-1 prevention trials. The Partners in Prevention HSV/HIV Transmission Study (ClinicalTrials.gov #NCT00194519) was a prospective randomized placebo-controlled trial that enrolled serodiscordant heterosexual couples to determine the efficacy of genital herpes suppression in reducing HIV-1 transmission; as part of the study analysis, HIV-1 sequences were examined for genetic linkage between seroconverters and their enrolled partners.
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Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons.
J. Infect. Dis.
PUBLISHED: 01-12-2011
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Recent in vitro studies suggest that acyclovir may directly inhibit HIV-1 replication and can select for a specific HIV-1 reverse transcriptase mutation (V75I) with concomitant loss of an anti-HIV-1 effect. We tested for HIV-1 genotypic resistance at reverse transcriptase codon 75 in plasma from 168 HIV-1-infected persons from Botswana, Kenya, Peru, and the United States taking daily acyclovir or valacyclovir for between 8 weeks and 24 months. No V75I cases were detected (95% confidence interval, 0%-2.2%). These prospective in vivo studies suggest that standard-dose acyclovir or valacyclovir does not select for HIV-1 resistance.
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Sexually transmitted infections and HIV: epidemiology and interventions.
Top HIV Med
PUBLISHED: 11-26-2010
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Although the association of HIV and sexually transmitted infections (STIs) has been well known for 25 years, there is insufficient attention to STIs by many HIV providers, in part because patients are asymptomatic or have nonspecific symptoms and because of provider demands and focus. Optimal patient care requires frequent testing for STIs as well as obtaining an accurate medical history, which requires building trust with patients and asking direct but open-ended questions about risks and symptoms. Increased vigilance will also help practitioners avoid missing these infections. Herpes simplex virus type 2 infection has highly variable clinical manifestations, and diagnosis is needed before considering episodic or suppressive treatment. However, suppressive treatment of herpes simplex virus type 2 infection has not been shown to reduce risk of HIV acquisition. The increase in syphilis rates continues; screening is inexpensive and treatment is highly effective. Quinolone resistance rates in gonorrhea are increasing, complicating treatment in some locales. Cases of proctitis caused by chlamydial infection with lymphogranuloma venereum strains have been observed in the United States and Europe.
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Treatment of sexually transmitted infections for HIV prevention: end of the road or new beginning?
AIDS
PUBLISHED: 11-03-2010
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Observational and biological data provide compelling evidence of the importance of sexually transmitted infections (STIs) in HIV transmission, but only one of nine intervention trials has shown an effect. This article reviews the observational studies, critically examines the nine randomized controlled trials evaluating the impact of STI treatment interventions on HIV incidence, and discusses implications for HIV prevention policy, programs and future research. The role of other vaginal infections is also briefly considered. In aggregate, the evidence strongly supports the concept that STI treatment prevents HIV infection. However, issues in trial design and conduct, including HIV epidemic phase, STI prevalence, intervention in comparison groups, and power have affected five of the six trials of treatment of curable STIs. In the three herpes intervention trials, antivirals for HSV suppression were insufficiently potent to alleviate persistent genital inflammation in HIV-negative HSV2-positive persons, and the reduction in HIV levels in HIV-positive persons was insufficient to reduce HIV transmission. It is time for a new phase of exploration of how, when, and in whom to include STI control as a key component of HIV prevention, driven by basic research to elucidate the mechanisms by which STIs and vaginal infections facilitate HIV transmission. From a policy perspective, treatment of curable STIs is an essential part of primary healthcare and is a cheap, simple, and effective intervention when appropriately targeted and delivered. It should be promoted as an essential component of HIV control programs in communities in which the burden of STIs is substantial.
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Will circumcision provide even more protection from HIV to women and men? New estimates of the population impact of circumcision interventions.
Sex Transm Infect
PUBLISHED: 10-21-2010
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Mathematical modelling has indicated that expansion of male circumcision services in high HIV prevalence settings can substantially reduce population-level HIV transmission. However, these projections need revision to incorporate new data on the effect of male circumcision on the risk of acquiring and transmitting HIV.
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Use of acyclovir for suppression of human immunodeficiency virus infection is not associated with genotypic evidence of herpes simplex virus type 2 resistance to acyclovir: analysis of specimens from three phase III trials.
J. Clin. Microbiol.
PUBLISHED: 08-11-2010
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Herpes simplex virus type 2 (HSV-2) is the most common cause of genital ulcer disease and is a cofactor for HIV-1 acquisition and transmission. We analyzed specimens from three separate phase III trials of acyclovir (ACV) for prevention of HIV-1 acquisition and transmission to determine if failure of ACV to interrupt HIV acquisition and transmission was associated with genotypic ACV resistance. Acyclovir (400 mg twice daily) or placebo was provided to HSV-2-infected persons at risk of HIV-1 infection in the Mwanza and HPTN 039 trials and to persons dually infected with HSV-2 and HIV-1 who had an HIV-negative partner in the Partners in Prevention study. We extracted HSV DNA from genital ulcer swabs or cervicovaginal lavage fluids from 68 samples obtained from 64 participants randomized to ACV and sequenced the HSV-2 UL23 gene encoding thymidine kinase. The UL23 sequences were compared with published and unpublished data. Variants were observed in 38/1,128 (3.4%) nucleotide positions in the UL23 open reading frame, with 58% of these encoding amino acid changes. No deletions, insertions, or mutations known to be associated with resistance were detected. Thirty-one of the variants (81.5%) are newly reported, 15 of which code for amino acid changes. Overall, UL23 is highly polymorphic compared to other loci in HSV-2, but no drug resistance mutations were detected that could explain the failure to reduce HIV incidence or to prevent HIV-1 transmission in these studies.
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Periconception pre-exposure prophylaxis to prevent HIV transmission: benefits, risks, and challenges to implementation.
AIDS
PUBLISHED: 08-04-2010
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HIV-serodiscordant couples face complicated choices between fulfilling reproductive desire and risking HIV transmission to their partners and children. Sexual HIV transmission can be dramatically reduced through artificial insemination and sperm washing; however, most couples cannot access these resources. We propose that periconception pre-exposure prophylaxis (PrEP) could offer an important, complementary therapy to harm reduction counseling programs that aim to decrease HIV transmission for couples who choose to conceive. In this paper, we describe the potential benefits of periconception PrEP and define critical points of clarification prior to implementation of PrEP as part of a reproductive health program. We consider sexual transmission risk, current risk reduction options, PrEP efficacy, cost, adherence, resistance, fetal toxicity, and impact of PrEP counseling on entry into health services. We address PrEP in the context of other periconception HIV-prevention strategies, including antiretroviral treatment of the HIV-infected partner. We conclude that, should PrEP prove safe and efficacious in ongoing trials, periconception PrEP may offer a useful approach to minimize risk of HIV transmission for individuals of reproductive age in HIV-endemic countries.
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Effect of acyclovir on HIV-1 set point among herpes simplex virus type 2-seropositive persons during early HIV-1 infection.
J. Infect. Dis.
PUBLISHED: 07-24-2010
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We evaluated whether acyclovir suppression during human immunodeficiency virus type 1 (HIV-1) acquisition reduces HIV-1 set point, increases CD4 cell counts, and selects reverse-transcriptase mutations among 76 HIV-1 seroconverters identified in a placebo-controlled trial of twice-daily acyclovir (400 mg) for the prevention of HIV acquisition in herpes simplex virus type 2 (HSV-2)-seropositive persons (HIV Prevention Trials Network study 039). We found no significant difference in plasma HIV-1 RNA levels (P =.30) or CD4 cell counts (P =.85) between the acyclovir and placebo recipients. V75I and other mutations in HIV-1 reverse transcriptase reported from in vitro acyclovir studies were not observed. In conclusion, acyclovir suppression during HIV-1 seroconversion and the subsequent 6 months does not affect HIV-1 set point.
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A prospective study of contraceptive use among African women in HIV-1 serodiscordant partnerships.
Sex Transm Dis
PUBLISHED: 07-06-2010
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Dual contraception is important for averting HIV-1 transmission, unintended pregnancy, and maternal-to-child HIV-1 transmission. Few studies have explored contraceptive use in HIV-1 serodiscordant couples, a population at high risk for HIV-1 transmission.
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Genital ulcer disease treatment policies and access to acyclovir in eight sub-Saharan African countries.
Sex Transm Dis
PUBLISHED: 06-12-2010
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Herpes simplex virus-2, the most common cause of genital ulcer disease (GUD) globally, is a cofactor in human immunodeficiency virus type-1 (HIV-1) acquisition and transmission. Current World Health Organization guidelines for sexually transmitted infections recommend acyclovir as first-line syndromic treatment of GUD in countries with high herpes simplex virus-2 prevalence (> or =30%).
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Estimating the impact of plasma HIV-1 RNA reductions on heterosexual HIV-1 transmission risk.
PLoS ONE
PUBLISHED: 06-10-2010
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The risk of sexual transmission of HIV-1 is strongly associated with the level of HIV-1 RNA in plasma making reduction in HIV-1 plasma levels an important target for HIV-1 prevention interventions. A quantitative understanding of the relationship of plasma HIV-1 RNA and HIV-1 transmission risk could help predict the impact of candidate HIV-1 prevention interventions that operate by reducing plasma HIV-1 levels, such as antiretroviral therapy (ART), therapeutic vaccines, and other non-ART interventions.
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Heterosexual HIV-1 transmission after initiation of antiretroviral therapy: a prospective cohort analysis.
Lancet
PUBLISHED: 05-26-2010
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High plasma HIV-1 RNA concentrations are associated with increased risk of HIV-1 transmission. Initiation of antiretroviral therapy (ART) reduces plasma HIV-1 concentrations. We aimed to assess the effect of ART use by patients infected with HIV-1 on risk of transmission to their uninfected partners.
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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.